1. Field
The present invention is generally directed to compositions and methods for treating BH4-responsive disorders, and methods and compositions for detecting and quantitating biopterins.
2. Background of the Related Technology
Tetrahydrobiopterin (referred to herein as BH4) is a biogenic amine of the naturally-occurring pterin family that is a cofactor for a number of different enzymes, including phenylalanine hydroxylase (PAH), tyrosine hydroxylase, tryptophan hydroxylase and nitric oxide synthase. Pterins are present in physiological fluids and tissues in reduced and oxidized forms, however, only the 5,6,7,8, tetrahydrobiopterin is biologically active. It is a chiral molecule and the 6R enantiomer of the cofactor is known to be the biologically active enantiomer. For a detailed review of the synthesis and disorders of BH4 see Blau et al., 2001 (Disorders of tetrahydrobiopterin and related biogenic amines. In: Scriver C R, Beaudet A L, Sly W S, Valle D, Childs B, Vogelstein B, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York: McGraw-Hill, 2001: 1275-1776).
Fiege, et al., Molecular Genetics and Metabolism 81:45-51 (2004) studied pharmacokinetics of orally administered tetrahydrobiopterin (BH4) and suggested a “rather large variability of orally administered BH4, probably due to different absorption in the gut and/or to the first passage effect.”
Use of tetrahydrobiopterin has been proposed for treating a variety of different disease states, and there exists a need for alternative and improved methods of administering this drug.